Abstracts

Rationale: Inflammatory cyclooxygenase-2 (COX-2) enzyme is induced by epileptic seizures, regulates neuronal excitability and synaptic plasticity, and is associated with neuronal death. The aim of this study was to determine if treatment with COX-2 inhibitor improves outcome at 24 h after pilocarpine-induced status epilepticus in rats. Methods: Surface EEG electrodes were implanted in 25 male Sprague-Dawley rats. After a 1-week recovery period, status epilepticus was induced by intraperitoneal injection of lithium-pilocarpine, and continuous EEG-video monitoring was performed for 24 h. At 30 min after the first seizure, COX-2 inhibitor (NS-398, 10 mg/kg, i.p.) was injected in 11 rats (NS-398-group), while 14 rats received the vehicle (control group). Surviving animals were perfused at 24 h after induction of status epilepticus. FluoroJade staining and COX-2 immunostaining were conducted on every third coronal section (40 μm) of the dorsal hippocampus. Quantitative analysis of the FluoroJade-stained cell number was performed in three predefined fields (0.2 mm x 0.2 mm each) of the CA1, CA3 and hilus of the dentate gyrus. Results: Only 1 rat died in the NS-398 group (9.1%) vs. 4 rats in the control group (28.6%); thus, these data suggest that mortality rate at 24 h was decreased in rats treated with the COX-2 inhibitor. So far, neuronal death has been analyzed in 4 rats/group, and neuroprotection has been observed in the CA3 area and the hilus of the dentate gyrus in rats treated with COX-2 inhibitor. Conclusions: Our present data suggest that COX-2 inhibition improves functional outcome and survival after status epilepticus, and may provide a neuroprotective strategy for status epilepticus. Supported by N01-NS-4-2359 from NIH.